Angelman Syndrome, Tristan Burkitt's Journey with AS

 

Understanding AS

Angelman syndrome (AS) is a neuro-genetic disorder that occurs in one in 15,000 live births. AS is often misdiagnosed as cerebral palsy or autism. Characteristics of the disorder include developmental delay, lack of speech, frequent laughter or smiling, and usually a happy demeanor, seizures, and walking and balance disorders. Individuals with Angelman syndrome will require life-long care.

 

 

Genetic Mechanisms of Angelman Syndrome

 

Normal 15 Chromosome

We each have two number 15 chromosomes, one inherited from our mother (M.) and one inherited from our father (P, paternal). The Angelman syndrome gene (UBE3A) is located at chromosome 15, band q12, as depicted. In the brain, the Angelman gene is primarily expressed from the maternally inherited chromosome 15. The diagram below illustrates the known genetic mechanisms that cause Angelman syndrome.

 

 

 

(The way Tristan got Angelman)

 

Paternal Uniparental Disomy (UPD) – 3%

In this case, Angelman syndrome is caused by the presence of two, normal paternally derived number 15 chromosomes. Since the maternally derived chromosome is absent (and it is the one that expresses the Angelman gene in the brain) Angelman syndrome occurs.

Laboratory Testing

This abnormality can also be screened for the DNA methylation test. Confirmation of UPD however requires further genetic molecular study. Use of polymorphic DNA markers for chromosome 15 is used to identify whether both chromosomes are of paternal origin.

 

 

 

TESTING FOR AS

 

Step 1. Methylation Test. The most useful diagnostic test. If this is "positive" i.e. the methylation pattern is characteristic of Angelman syndrome, then the diagnosis is confirmed. The laboratory will then go on to determine whether the AS is due to a deletion, uniparental disomy or an imprinting defect. - This was Tristan's Positive

 

Step 2 FISH test. - a specialised type of chromosome analysis which will detect very tiny abnormalities, normally invisible on routine examination The FISH test is a way of testing the chromosomes to check for a deletion. If the methylation test is positive and the FISH test is positive no further tests are needed as the diagnosis of deletion positive AS is confirmed.

 

Step 3 RFLP analysis. (DNA test to check that a chromosome 15 has been inherited from each parent) If methylation is positive but FISH is negative RFLP analysis will be used to differentiate between AS due to uniparental disomy and AS due to an imprinting defect. With UPD both chromosome 15s will have come from the father. With an imprinting defect both parents will have contributed a chromosome 15. If RFLP analysis confirms UPD no further tests are needed.

 

Step 4 Search for imprinting centre mutations. If methylation test was positive and neither deletion or UPD were present then there is an imprinting defect. In some families, in order to offer accurate genetic counselling, it is then necessary to look for the precise change or "mutation" on chromosome 15 which gave rise to the imprinting defect. Only a couple of laboratories in the world offer this type of testing at present.

 

Step 5 UBE3A screening. If methylation was normal but Angelman syndrome is still strongly suspected clinically i.e. the movements and behaviour are typical and there is a characteristic EEG pattern then the next step is to screen the UBE3A gene to look for a tiny change within the gene. This is a laborious and expensive process but worth trying in selected patients as mutations will be detected in 20% (80% if familial Angelman syndrome).

 

Step 6 Consider other possibilities. If all the tests above are negative, then Angelman syndrome is unlikely, though not impossible. Other diagnostic possibilities should be considered and it is recommended that patients be reviewed by a paediatrician/neurologist from time to time as the situation may change or new tests may become available over the years.

 

 

♥ABOUT TRISTAN♥

Tristan was born on August 12, 2010, 7 lbs 4 oz 20" healthy newborn, passed his newborn screening, not fussy- a very content newborn baby boy!

When we got home from the hospital, we noticed his feeding was getting worse, constently spitting up, not gaining weight, not sleeping (maybe an hour out of 24 hours), screaming, he stayed as stiff as board ALL the time, constent fussiness and just an all around a "Mad Baby".

 

We took him to his pediatrition on a weekly basis- weight checks and eating concerns, his doctor kept telling us he was just a fussy baby and basically "suck it up", she said he had reflux (which I told her the last 4x we saw her) and started him on reflux meds at 3 1/2 wks old. His eating got worse and sleepless nights were endless, finally at 1 month 1 day old he had gotten to the point that he refused to eat AT ALL, I fed him with a 1ml syringe when he refused to eat that morning. I said enough is enough and took him back to his doctor that morning and told her if she couldnt do anything for us we were going to the ER, she looked him over again and said since he still hadnt gained weight (still 7 lbs) and was refusing to eat she would call the hospital and get him admitted!

 

We then drove to the hospital, where he was admitted right away, they began doing testing on him for infections, auto ammune disorders, and the list goes on. When the doctors saw him they were stunned when all results kept coming back negative, they told me "we know something is wrong with your child and he's in pain, we just cant figure out what." He was Inpatient for 4 1/2 months with test after test again all negative, the only thing he was ever diagnosed with at the time was "the most severe reflux the hospital had ever seen" and Laryngomalacia (immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction.) which also caused and is still causing freguent bronchitis, he was put on an NG tube as soon as he was admitted and 1 month later went in for surgery for a Mic-Key Button (G-tube). While in the hospital he had everything from lab work to full body scans and 3 Spinal Taps! Neurology, Genetics, Rehab, GI, Ear Nose & Throat, And ALL the doctors in between consulted him and everyone still kept ruling things out but couldnt find a cause for his "Pain" and discomfort!

At 5 months we finally went home without any answers, but Tristan was a little more content than his normal.

 

We began to see over the next few months he wasnt advancing, we started therapy (PT & OT) that came to the house to work with him weekly, but even with therapy we werent seeing the improvment they told us he should be having. He sat up at 7 months, starting "army" crawling at 11 months, crawled on hands and knees at 14 months and is now pulling up on furniture at 20 months :)

We kept following up with all the doctors and they all said he was improving and there was no need to run anymore test, that now he just needed to play "catch-up". After a few months of the Mic Key button his personality started to change and he became the happiest baby boy in the WORLD! all smiles and laughter, but never made any sound (Babble)

 

He is in LOVE with water and started to eat baby food then finger foods at 7 months+ and did so good we were able to get his Mic Key button taken out on March 26, 2012!!!

 

I called genetics in Feb. to see about a follow-up since it had been close to a yr since we had seen them, and they scheduled for us to come in and see where Tristan was in his progession. After talking with his Genetics consulor and Doctor they decided to do more lab work and check for a few more rare Diagnosis, one week later on April 23, 2012 I got a phone call that Tristan had Angelman Syndrome! (Now they did genetic testing on him when he was inpatient but only looking at the initial testing was normal because again, his form is very uncommon and they have to specifically look at chromosome 15)

 

The phone call was such a mix of emotions!!! SO HAPPY to finally have an answer and know what to work towards and what therapy we needed to be focusing on, but that was the hardest diagnosis to get, I started uncontrolably crying and didnt know what to think or feel, picturing the future I had planned out in my head so many times for him and knowing our lives would change forever!

 

Once I got myself back together and realized this isnt the end of the world and me being down wasnt going to solve anything, I started to imagine a differnt future with differnt goals to achieve and new dreams to strive for. My son is not his diagnosis and I will not let anyone tell him he cant do something, he is the strongest willed child I have ever met and he WILL achieve anything he sets his mind to and Im just waiting for the day, whether its tomorrow or 5 yrs from now, that he takes his 1st steps and says his 1st word.

 

Tristan's smile and laugh makes anyone that comes in contact with him light up, he is the sweetest,most loving, sensitive little boy I know and I will be his advicator and voice and fight to find a cure for all children with AS and live each day to its fullest with hope in my heart and my family by my side.

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♥I AM THE DISABLED CHILD ♥

I am the child who cannot talk.
I am the child who cannot walk.

You often pity me. I see it in your eyes. You wonder how
much I am aware of...I see that as well. I am aware of much...
whether you are happy or sad or fearful, patient or
impatient, full of love and desire, or if you are just doing
your duty by me. I marvel at your frustration, knowing mine

to be far greater, for I cannot express myself nor my needs as you
do. You cannot conceive my isolation, so complete it is at times.
I do not gift you with clever conversation, cute remarks
to be laughed over and repeated. I do not give you answers to
your everyday questions, responses over my well-being, sharing my
needs, or comments about the world around me. I do not give
you rewards as defined by the world's standards...great
strides in development that you can credit yourself. I do not
give you understanding as you know it. What I give you
is so much more valuable..I give you instead opportunities.
Opportunities to discover the depth of your character, not mine;
the depth of your love, your commitment, your patience, your
abilities; The opportunity to explore your spirit more deeply than
you imagined possible. I drive you further than you ever go
on your own, working harder, seeking answers to your
many questions, creating questions with no answers.

The world sometimes seems to pass me by. You see the
longing in my eyes to get out of this chair, to run and play
like other children. There is much you take for granted. I want the
toys on the top shelf. I need to go to the bathroom...oh...
I've dropped my spoon again. I am dependent on you in
these ways. My gift to you is to make you aware of your
great fortune, your healthy back and legs, your ability to do
for yourself. Sometimes people appear not to notice me; I
always notice them. I feel not so much envy as desire, desire
to stand upright, to put one foot in front of the other, to
be independent. I give you awareness.

I am the child who cannot walk.
I am the child who is mentally impaired.

I don't learn easily, if you judge me by the world's
measuring stick. What I do know is infinite joy in the
simple things. I am not burdened as you are with the
strifes and conflicts of a more complicated life. My
gift to you is to grant you the freedom to enjoy things
as a child, to teach you how much your arms around
me mean, to give you love. I give you the gift of simplicity.
I am the disabled child.
I am your teacher. If you allow me, I will teach you what is really important in life.

I will give you and teach you unconditional love.
I give to you my innocent trust, my dependency upon you.
I teach you of respect for others and their uniqueness.
I teach you about the sanctity of life.
I teach you about how very precious this life is and
about not taking things for granted.
I teach you about forgetting your own needs and desires and dreams.
I teach you giving.
Most of all, I teach you hope and faith.

I am the disabled child